Search

The utility of the light-emitting diode (LED) matrix, i.e. the qualitative localization of maxima and minima in the patterns of the specific absorption rate (SAR), can be extended to quantitative measurements by a method described. With the LED dipoles on the matrix representing light sources of similar characteristics, the minimal field strength necessary to produce light is a criterion which can be easily determined. From the power levels necessary to fulfil this criterion, relative SAR values have been calculated. The attenuation of field strength by the LED matrix has been measured by an additional dipole antenna with fibre-optic read-out, so that the calculated SAR profiles could be corrected for the relatively smaller attenuation near the edges. This technique has been tested for several set-ups in a 'Coaxial TEM applicator' and the resulting SAR profiles along the major axis of the aperture midplane were compared with SAR profiles determined using a single dipole E-field probe. Results show that, from a set of photographs at different power levels, SAR profiles can be constructed with limited accuracy along lines in any direction in the whole aperture midplane and by this the complete two-dimensional SAR pattern can be obtained.

The cervical region of the rat, including the spinal cord (cervical 5-thoracic 2) was irradiated with single doses of 15-32 Gy 250 kV X-rays. Hyperthermia, at temperatures of 42-, 43- and 44 ± 0·1°C for 30 min was applied to the cervical vertebral column and immediate adjacent tissues for 5-10 min or 7 h after X-irradiation. Over a period of 18-21 months, animals were followed up to monitor neurological complications occurring as a result of damage to the spinal cord (Sminia et al. 1991). We also noted the development of neoplasms either inside or outside the cervical region. The data on tumour incidence were analysed retrospectively using the actuarial method. Although hyperthermia alone was not carcinogenic, it led to a significant increase of radiation-induced tumours. This increase of radiation carcinogenesis was observed both with hyperthermia applied 5-10 min after X-rays and with an interval of 7 h between X-rays and heat. Cancer induction was highest after the lower radiation doses (16 Gy) combined with high heat doses (30 min 44°C). The latent period for induction of tumours by X-rays was 472 ± 19 days (mean ± SEM; n = 24). Latency was significantly shortened by hyperthermia to 404 ± 34 days (n = 22) if applied 5-10 min after X-rays and to 348 ± 6 days (n = 33) with an interval of 7 h. Histology revealed that 86% (38/44) of the examined tumours found inside the volume treated with hyperthermia and irradiation were sarcomas. The percentage of animals with a tumour outside the treated volume was almost the same for all treatment groups. Most of these tumours were of the mammary gland type.

The incidence of tumours in the irradiated cervical region in female Wistar (WU) rats after retreatment of part of the volume with hyperthermia was examined retrospectively. The cervical spinal cord (cervical 5-thoracic 2) was irradiated with a single dose of 15, 18 or 20 Gy. Ninety days thereafter, the cervical region was heated by means of a microwave applicator at a maximum temperature of 43°C for 50-90 min measured at the vertebral column. Over a period of 18 months after treatment, animals were regularly observed. Neurological complications and the development of neoplasms were noted. From the 354 animals included in the study, 82 animals developed a tumour. Hyperthermia alone was not carcinogenic, but enhanced the carcinogenesis induced by radiation. The percentage of animals that developed a tumour inside the volume treated with hyperthermia 90 days after irradiation was significantly higher relative to radiation alone (33 ± 5 per cent versus 4 ± 2 per cent, P < 0·001). The duration of the latent period before appearance of these tumours was not affected (355 ± 18 days versus 425 ± 54 days). No significant differences in the percentage of animals that developed a tumour at another site were observed between different treatment groups. Histology revealed that 88 per cent (14/16) of the examined tumours found inside the treated volume after hyperthermia and irradiation were soft tissue rhabdomyosarcomas. Outside the treated volume, most tumours were tumours of the mammary gland.

The capability of self-regulating thermoseeds to compensate for nonuniform cooling along their longitudinal axis has been investigated in this study. For this purpose a quasi three-dimensional computer model has been developed. Calculations of the temperature profile in tissue with nonuniform heat loss demonstrated a clear improvement in the longitudinal temperature control of PdNi seeds compared to constant power seeds. Further, two strategies for improved control of nonuniform cooling along the longitudinal axis of ferromagnetic seeds have been investigated: (1) application of a 'normal' undivided seed; and (2) division of a long seed in smaller segments of which each segment is able to respond more directly to local variations in the temperature distribution. Calculations with the quasi three-dimensional model showed that the loose segments do respond more directly to their close proximity. However, the equilibrium temperature of a segment in an area with high local blood flow will be relatively low due the limited heat production of PdNi thermoseeds. In the undivided seeds the high thermal conductivity of PdNi causes some levelling of the longitudinal temperature gradient in the seed. In addition, calorimetric experiments have shown that the heat production of a segmented seed is less effective because of a demagnetizing field. Also, the absence of PdNi between the segments reduces the heat production of the seed.

In the development of materials for self-regulating thermoseeds much effort is put in improvement of the self-regulating temperature control mechanism of the seeds. The catheters and coatings which are needed to implant the seeds or to guarantee biocompatibility, generally impair the optimized performance of the ferromagnetic seeds. The influence of various coatings on the performance of PdNi seeds has been investigated by means of one-dimensional modelling and calorimetric experiments. Implantation using thin walled catheters is acceptable provided that the catheters are filled with water to assure good thermal coupling. Air layers inside catheters should be avoided as they reduce the sharp gradient of the heat production at the Curie temperature significantly. An alternative for the application of catheters is to insert the seeds into metallic needles. The effect of shielding by the metal needle can be minimized by driving the seed into its saturated state using a high magnetic field strength. The thermal interaction between the seed and surrounding tissue can also be enhanced by placing PdNi, e.g. tubular, on the outside of the catheter or brachytherapy needle. An additional advantage of this new design is an increase in the heat production and the quality of temperature control due to an increase in the amount of PdNi. For permanent implantation seeds can be coated with an inert metal, ceramics or plastic. The performance of the seeds is not affected by any of the coatings if certain conditions are met. For plastic coatings the thickness of the coating has to be very thin, preferably <<20 μm, to avoid thermal isolation.

A simple, unique tool has been constructed at a very low cost for visualization of the electric field distribution in a phantom exposed to radiofrequency fields from a four-applicator hyperthermia system. The tool consists of a thin Perspex plate to which light-emitting diodes (LEDs) have been attached in a regular pattern. The leads of these LEDs have been bent in the form of dipoles. Electric field distributions can be made visible, because the light intensity from an individual LED dipole in a RF field is a function of the local electric field strength. The LED dipoles were arranged in a 11 ± 15 matrix with a mutual distance of 2 cm. Experiments have been performed in a cylinder with a length of 100 cm and with an elliptical cross-section of 24 cm ± 36 cm. The cylinder was filled with saline to simulate the electric properties of biological tissue. The matrix plate was shaped like the cross-section inside the phantom, and could be moved to any position under the externally applied antennae. In our department the applicators installed form a system of four coherent waveguide radiators operating at a frequency of 70 MHz. Photographs have been taken from the distribution of the light intensity through transparent windows at the outer ends of the phantom. The advantage of the LED matrix is the fact that the effect of changing phase relations, amplitudes or position of any applicator on the electric field distribution can be seen instantaneously. The interference effects of multiple fields, i.e. extinction and reinforcement, become easily visible. Typical examples demonstrate the necessity to obtain the field distribution not only along some previously chosen lines, but in the whole transversal midplane. The attenuation of field strength due to the presence of the matrix varies only slightly from the edge to the centre of the matrix, so the pattern of light intensity is in good qualitative agreement with the pattern of field strength. The LED matrix has been very useful in the verification of pretreatment planning calculations, and is already used for intercomparison and evaluation studies of similar hyperthermia equipment.

The Effective Field Sizes (EPS) and the Effective Heating Depths (EDH) of Contact Flexible Microstrip Applicators (CFMA), tuned at a frequency of 434 MHz, were determined on two fat/muscle phantoms. One phantom was box-shaped with a flat top layer of 1 cm thick artificial fat and the other one a tube of which the cross-section was elliptically shaped (25 × 36 cm) having a fat equivalent shell of 1 cm thick. For the muscle material a 6 g/1 saline (NaCl) solution was used. On the flat rectangular phantom, the effective field size at 1 cm depth in saline was measured to be 4·7 × 13·5 cm, 17·5 × 17·7 cm and 12·5 × 14·0 cm for the 1H-applicator, the 3H-applicator and the 5H-applicator, respectively. For the 3H- and the 5H-applicator, the Specific absorption rate (SAR) distribution at 1 cm depth showed a single maximum of SAR for a thin bolus, which split into two separate 'hot spots' for a thicker bolus. The Effective Heating Depths in the phantom with a flat surface were of the order of that of a plane wave (∼ 1·4 cm), whereas a larger EHD of 2·4 cm was achieved below the 3H-applicator bent to fit the elliptical phantom. Due to the large effective field size and the 'flatness' of the SAR distribution, the applicators 3H and 5H are suitable to adequately treat large superficial tumours.

The limited aperture size through which the em-field of the applicator is emanated and the constraining of this em-field near the bolus' edge is related to the appearance of superficial 'hot spot' phenomena in radiative hyperthermia. Regarding systems based on the concept of the annular phased array two questions arise: (1) what is the relative strength of the radial component present in the incident field of the radiators, and (2) in what way are fringing fields related to the bolus size? To address both of the above questions, the spatial distribution of the em-field emanated through the aperture of an applicator of the Amsterdam four waveguide-array system has been investigated for a long bolus and a short bolus. The em vector field emanated by the applicator has been characterized in two perpendicular planes, i.e. the aperture midplane and the sagittal midplane. It should be noted that this distribution depends on the propagation conditions throughout the coupling bolus, the phantom and other volumes attached, such as other applicators. Therefore two sets of propagation conditions have been measured:(1) the minimum number of parameters determining the propagation of the em-field namely one single waveguide, one bolus and a homogeneous phantom, and(2) the propagation conditions as for the clinical setting. It is stressed that the study concerns one specific radiative hyperthermia system, namely the AMC four-waveguide array, but that, based on the similarities discussed above, results may be extrapolated towards other radiative hyperthermia systems. According to the current study, bolus prolongation might lead to a clear clinical improvement, which is due to a decrease of the fringing field amplitude compared to the field amplitude in the centre of the aperture midplane. Bolus prolongation will lead to an extended heating area, the field lines being more aligned to the patient's main axis.

The Amsterdam phantom with LED-matrix is applied as an instrument in testing the performance of four types of radiative deep-body hyperthermia systems, which are in clinical use in Germany and The Netherlands. The devices tested were Essen's BSD-1000, Berlin's BSD-2000, Utrecht's Coaxial TEM applicator and Amsterdam's Four-waveguide-array. Photographs were taken of the matrix of dipoles loaded with light-emitting diodes (LED) to visualize the distribution of the RF power deposition or specific absorption rate (SAR) in the aperture midplane. The utility of the phantom with LED matrix for various types of radiative hyperthermia systems is demonstrated.Within this preliminary study, the influence of important parameters on the SAR-pattern in the aperture midplane was demonstrated. After corrections on the phase relation of the applicators a central focus in the SAR distribution could be realized in all systems and could also be moved in any direction. The patterns of the central focus changed in its absolute values and its proportions depending on the relative relations of phase and amplitude of the lateral applicators with respect to the top and bottom applicator. Frequency dependency was recognized for the central focus of the BSD-1000 as well as for the irradiation pattern of a single applicator for the BSD-2000. In the Coaxial TEM applicator it was demonstrated that the dimension of the open water bolus influenced the absolute value of SAR in the aperture midplane.

The cervical spinal cord (C5-T5) of female Wistar WU rats was irradiated with 250 kV X-rays (15-32 Gy). Heat was applied at approximately the same site 7 ± 1 min after X-rays. 'Early delayed' paralysis of the forelegs was observed 5-10 months after treatment. The ED50 (± SE) after single-dose irradiation alone was 25·8 ± 0·4 Gy. 'Late delayed' paralysis and paresis were observed 11-21 months after irradiation with an ED50 (X-rays alone) of 22·7 ± 0·6 Gy. The data for late paralysis, late paresis and minor neurological symptoms were pooled resulting in an ED50 (± SE) of 20·6 ± 0·7 Gy. Hyperthermia enhanced the radiation response. Thermal enhancement ratios (TER) in the 'early delayed' response after a 30 min treatment with 41·1 ± 0·4°C, 42·1 ± 0·4°C and 42·9 ± 0·4°C were 1·07 ± 0·08, 1·17 ± 0·08 and 1·12 ± 0·04 respectively. For the 'late delayed' radiation response concerning paralysis and paresis the TER after 30 min at 41·1°C and 42·1°C were 1·25 ± 0·10 and 1·31 ± 0·07, respectively. The latent period for paralysis was not significantly affected. Pathological examination of the spinal cord after combined treatment of X-rays and hyperthermia showed focal demyelination with white matter necrosis and vascular injury in animals as an indication of 'early delayed' and 'late delayed' paralysis, respectively. This was not different from histopathological changes observed after irradiation alone.

The effect of local heat treatment of the sciatic nerve was assessed using the toe-spreading test, which mainly assesses the motor function of the sciatic nerve. A 5 mm long segment of the nerve was heated at temperatures from 42·0 to 45·0°C in vivo using a brass thermode. Hyperthermia led to a decrease in spreading of the toes. Recovery from functional loss took place in all cases, and this recovery was completed in 4 weeks. A 50 per cent functional loss in 50 per cent of the treated animals was observed after 58, 32 and 12 min of heating at 43·0, 44·0 and 45·0°C respectively.